15-deoxy-Δ12,14-prostaglandin J2 inhibits the expression of microsomal prostaglandin E synthase type 2 in colon cancer cells
- Prostaglandin (PG) E2 (PGE2) plays a predominant role in promoting colorectal carcinogenesis. The biosynthesis of PGE2 is accomplished by conversion of the cyclooxygenase (COX) product PGH2 by several terminal prostaglandin E synthases (PGES). Among the known PGES isoforms, microsomal PGES type 1 (mPGES-1) and type 2 (mPGES-2) were found to be overexpressed in colorectal cancer (CRC); however, the role and regulation of these enzymes in this malignancy are not yet fully understood. Here, we report that the cyclopentenone prostaglandins (CyPGs) 15-deoxy-Δ12,14-PGJ2 and PGA2 downregulate mPGES-2 expression in the colorectal carcinoma cell lines Caco-2 and HCT 116 without affecting the expression of any other PGES or COX. Inhibition of mPGES-2 was subsequently followed by decreased microsomal PGES activity. These effects were mediated via modulation of the cellular thiol-disulfide redox status but did not involve activation of the peroxisome proliferator-activated receptor γ or PGD2 receptors. CyPGs had antiproliferative properties in vitro; however, this biological activity could not be directly attributed to decreased PGES activity because it could not be reversed by adding PGE2. Our data suggest that there is a feedback mechanism between PGE2 and CyPGs that implicates mPGES-2 as a new potential target for pharmacological intervention in CRC.
Author: | Oliver SchröderGND, Yulyana YudinaGND, Alan SabirshORCiDGND, Nadine Zahn, Jesper Z. HaeggströmORCiD, Jürgen SteinORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-755368 |
DOI: | https://doi.org/10.1194/jlr.M600008-JLR200 |
ISSN: | 0022-2275 |
Parent Title (English): | Journal of lipid research |
Publisher: | Elsevier |
Place of publication: | Amsterdam |
Document Type: | Article |
Language: | English |
Year of Completion: | 2006 |
Year of first Publication: | 2006 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2023/09/12 |
Tag: | colorectal cancer; cyclopentenone prostaglandins; feedback control; proliferation; prostaglandin E; redox status |
Volume: | 47 |
Issue: | 5 |
Page Number: | 10 |
First Page: | 1071 |
Last Page: | 1080 |
HeBIS-PPN: | 514232781 |
Institutes: | Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |